The field of cell biology has seen an enormous expansion in the area of "growth factors" or other protein and glycoproteins which influence the manner and degree to which cells react to various stimuli. One family of these (glyco)proteins, known as the cytokines, either directly or indirectly mediates host cell defense mechanisms or tissue growth differentiation. Among the materials so identified are the interferon family (INF-.alpha., INF-.beta., and INF-.gamma., transforming growth factor (TGF), tumor necrosis factor (TNF), the various colony stimulating factors such as "M-CSF" or "macrophage colony stimulating factor", "G-CSF" or "granulocyte colony stimulating factor", and "GM-CSF" or "granulocyte macrophage, colony stimulating factor". A growing family includes the "interleukins", which are generally referred to as "IL-X", where "X" is a whole number. This application concerns a new interleukin, referred to hereafter as "IL-9".
The literature on these proteins and glycoproteins, be it patent, technical or popular, is vast. Exemplary of the patent literature in this field are U.S. Pat. Nos. 4,851,512 (IL-2 derivatives), 4,863,727 (therapeutic use of IL-2 in combination with TNF), and U.S. Pat. Nos. 4,774,320; 4,772,685; 4,762,914; 4,681,844, and 4,404,280, all of which relate to some degree to IL-1. Also of interest are U.S. Pat. Nos. 4,810,643 and 4,833,127, relating to G-CSF, and U.S. Pat. Nos. 4,676,983, 4,530,784, and 4,431,582, relating to various cell growth and contact factors. Examples of the popular literature in the field include Smith, "Interleukin-2" in Scientific American 262(3): 50-57 (March, 1990), and Old, "Tumor Necrosis Factor" in Scientific American 258(5): 59-75 (May, 1988).
The above identified patent application, i.e., Ser. No. 07/246,582, to Van Snick et al., the disclosure of which is incorporated by reference, taught the discovery of a T cell growth factor which was produced by helper T cells, having a molecular weight of from about 30 to 40 kilodaltons and an isoelectric point of about 10. This factor would cause T cells, such as helper T cells, to proliferate when the factor was incubated with the T cells. The proliferation and growth of the T cells was IL-2 and IL-4 independent, and was also independent of antigen presence. As described therein the "P40" as it was called, was purified from the supernatant of lectin stimulated mouse helper T cells. The amino acid sequence of the protein and the DNA sequence expressing it were also described.
In a subsequent, continuation in part application, i.e., Ser. No. 07/408,155, filed Sep. 15, 1989, the disclosure of which is incorporated by reference, and in a further continuation in part, i.e., Ser. No. 07/462,158 filed Jan. 8, 1990, the disclosure of which is incorporated by reference, additional data on P40 were presented. This additional data include information on the human protein and the DNA sequence expressing the human protein. Additionally, these data can be reviewed in, e.g., Uyttenhove, et al., Proc. Natl. Acad. Sci. USA 85: 6934 (1988); Van Snick, et al., J. Exp. Med. 169: 363 (1989); Yang, et al., Blood 74: 1880 (1989). The disclosures of these last three papers are all also incorporated by reference herein. Additional data, as described by Schmitt, et al., Eur. J. Immunol. 19: 2167-2170(1989), show that P40 is apparently identical to "T cell Growth Factor III" ("TCGF III"), and is not a general T cell growth factor. The Schmitt paper is also incorporated by reference herein.
An additional factor of interest has been referred to in the literature as having "Mast Cell Growth Enhancing Activity". This factor was derived from pokeweed mitogen stimulated mouse spleen cell conditioned medium. This factor, and a partial purification thereof, are described in Hultner, et al., J. Immunol. 142: 3440-3446 (May 15, 1989), and Moeller, et al., J. Immunol. 142: 3447-3451 (May 15, 1989). Both of these disclosures are also incorporated by reference.
The Moeller paper, as attested to by its title, described partial purification of the factor, referred to as MEA hereafter. The partially purified material, which showed mast cell growth enhancing activity, was characterized by a molecular weight of from about 37 to about 43 kilodaltons, and an isoelectric point of from 6.2 to 7.3. The partially purified material was found to stimulate bone marrow mast cells, and, in the presence of IL-3, acted synergistically with respect to the proliferating effect on bone marrow mast cells. It was later found that the partially purified material could also sustain proliferation of a murine IL-3 dependent mast cell line in the absence of both IL-3 and IL-4. See, Hultner, et al., Exp. Hematol. 17: 1578 (1989), the disclosure of which is incorporated by reference.
Upon purification to homogeneity, it was found, unexpectedly, that MEA is identical to the factor previously reported as P40. It has also been found, surprisingly, that P40 has the same proliferative effect on mast cells as does MEA. The similarity of properties, characteristic of the interleukin cytokines, suggests that the materials be referred to as interleukin-9 ("IL-9" hereafter), and the invention relates to a method for enhancing the growth or proliferation of mast cells using the purified material, i.e., the "IL-9". For convenience hereafter, the IL-9 will be referred to in terms of its molecular weight and isoelectric point characteristics, i.e., a molecular weight of from about 30 to 40 kilodaltons, and an isoelectric point of about 10. Unless stated to the contrary, reference to "MEA" means MEA purified to homogeneity.